Patients with metastatic osteosarcoma are unlikely to be cured. Sadly, immunotherapy has not yet proven effective for osteosarcoma for unknown reasons.
We investigated osteosarcoma samples which had spread to the lungs. These lung tumors are important because these are ultimately what kill patients. We found that these lung tumors “exclude” the body’s immune system through multiple mechanisms, including the presence of “pro-tumor” immune cells which shut down anti-tumor immune cells.
We have developed an RNA-nanoparticle vaccine. Simply put, we package genetic information from a patient’s osteosarcoma in a way that allows the immune system to recognize and destroy the cancer. These nanoparticles work in part by reprogramming those pro-tumor immune cells into anti-tumor immune cells—this means that for the first time, we are proposing to use a drug which can overcome the specific mechanisms that have so far prevented immunotherapy to be effective.
Excitingly, this drug has recently entered clinical trials in human patients with brain tumors. This drug is currently being studied in canine clinical trials in osteosarcoma. We thus propose performing experiments on the blood and tumor samples from canine patients with osteosarcoma to better understand how our nanoparticle activates the immune system. With this better understanding of how this drug works against osteosarcoma, we will be able to swiftly move this exciting new drug into clinical trials against osteosarcoma. We will also study this novel drug in combination with another class of drugs known as immune checkpoint inhibitors in canines with osteosarcoma. Immune checkpoint inhibitors are also currently being used to treat other types of cancer, and could be combined with nanoparticle vaccines in a future combination immunotherapy clinical trial.